Identification of noncoding RNA-encoded proteins on lipid droplets  

脂滴上noncoding RNA编码蛋白的发现与鉴定

作　　者：Ting Huang Adekunle T.Bamigbade Shimeng Xu Yaqin Deng Kang Xie Ololade O.Ogunsade Ahmed Hammad Mirza Jifeng Wang Pingsheng Liu Shuyan Zhang 黄婷;Adekunle T.Bamigbade;徐式孟;邓亚琴;解康;Ololade O.Ogunsade;Ahmed Hammad Mirza;王继峰;刘平生;张淑妍(School of Basic Medical Sciences,Southwest Medical University,Luzhou 646000,China;National Laboratory of Biomacromolecules,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China;University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]School of Basic Medical Sciences,Southwest Medical University,Luzhou 646000,China [2]National Laboratory of Biomacromolecules,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [3]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Science Bulletin》2021年第4期314-318,M0003,共6页科学通报（英文版）

基　　金：supported by the National Key Research Development Program of China(2018YFA0800900,2016YFA0500100,and 2018YFA0800700);the National Natural Science Foundation of China(31671402,91954108,91857201,31671233,31701018,and U1702288);the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA12040218)。

摘　　要：With the rapid development of high-throughput sequencing technologies,it has recently become evident that the eukaryotic genome is extensively transcribed[1,2].Large-scale projects for the systematic annotation and functional characterization of genes,such as GENCODE and FANTOM,have demonstrated that at least 80%of mammalian genomic DNA is actively transcribed.It has become increasingly clear that many genomic regions classified as noncoding actually harbor short open reading frames(sORFs)with fewer than 300 nucleotides,encoding small,functional proteins or micropeptides.These small proteins have evaded detection due to their small size,low abundance,instability,and loss during sample preparation[3].However,emerging experimental techniques,including ribosome profiling and mass spectrometry,along with computational advances have enabled their discovery and analysis[3,4).Most have been identified in prokaryotic organisms[4],but a growing number have also been discovered in eukaryotic organisms,including plants,zebrafish,insects,mice,and humans[2-4].These proteins have been found to play important roles in many fundamental biological processes[3]and have been reported to localize to cellular compartments such as mitochondria[5],late endosomes/lysosomes[6],and endoplasmic reticulum[7].However,given the large number of putative proteins encoded by noncoding RNAs,there is a need for much more investigation.In particular,there is a need for more information on the subcellular localization of these proteins,which may provide insight into their biological functions.研究表明,许多过去被注释为非编码的RNA,都可能具有编码蛋白的能力.目前已发现了数十个定位于不同细胞器的这类蛋白,它们在多个生物学过程中发挥着重要作用.脂滴(lipid droplet,LD)是一种由单层磷脂膜及外周蛋白包被中性脂核心的独特细胞器.脂滴与细胞脂质稳态的维持,以及人类代谢疾病的发生发展关系密切.而脂滴上是否存在由非编码RNA编码的蛋白仍然未知.本文发现了这类蛋白在脂滴上的存在,并进行了鉴定.作者从纯化的脂滴入手,通过富集小分子量蛋白,利用质谱学方法,发现了15个脂滴相关的非编码RNA来源的新蛋白(LD-associated noncoding RNA-encoded proteins,LDANPs).对LDANP1的进一步研究,确认了LDANP1定位在脂滴上,验证了其内源性表达,同时发现骨骼肌细胞中的LDANP1能够影响脂质贮存以及胰岛素信号.非编码RNA来源的蛋白在脂滴上的发现,为脂滴生物学,以及脂质代谢和代谢疾病的研究提供了崭新的思路及方向.

关 键 词：代谢疾病 非编码RNA 中性脂 质谱学 骨骼肌细胞 脂质代谢 磷脂膜 细胞脂质 

分 类 号：Q75[生物学—分子生物学]